Mr. Peabody is a gifted anthropomorphic dog who lives in a penthouse in New York City and raises his adopted human son, 7-year-old Sherman, and tutors him traveling throughout history using the WABAC, pronounced "way back", a time machine. They visit Marie Antoinette in Versailles during the French Revolution in 1789. Getting caught in the Reign of Terror, Peabody is nearly sent to the guillotine to be executed by Maximilien Robespierre, but escapes with Sherman through the Paris sewers.

In the present-day Sherman attends Susan B. Anthony school but his behavior has become a source of concern of school staff since he was raised by a dog. Showing the school that Mr. Peabody has actually taught Sherman a lot, they invite Sherman's love interest Penny over for a trip with the WABAC machine only to get involved in a series of conflicts that forever change the course of history. Based on the "Peabody's Improbable History" segments from The Rocky & Bullwinkle Show".